070 - Microenvironmental interactions and clinical behaviour in chronic lymphocytic leukemia: the CD49d lesson
Autor(s): D. Benedetti, A. Zucchetto, P. Bulian, C. Tripodo, R. Bomben, M. Dal Bo, G. Del Poeta, F.M. Rossi, M. Degan, F. Tedesco, S. Deaglio, F. Malavasi, V. Gattei
Issue: RIMeL - IJLaM, Vol. 6, N. 3-S1, 2010 (MAF Servizi srl ed.)
Page(s): 70-73
The results that will be presented take advantage of previous studies of gene expression and surface antigen expression profiles, identifying CD49d expression as a negative prognosticator for CLL patients, often in association with CD38 expression and an unmutated mutational status of IGHV genes, both negative prognostic markers in CLL. Altogether, the results that will be discussed contribute to define a model of interaction between CLL cells and the microenvironment. According to this model, CD38/CD49d-expressing CLL cells release two specific chemokines (CCL3 and CCL4) upon CD38 triggering by its natural counter-receptor CD31. CCL3 and CCL4 are eventually capable to recruit TNF-producing macrophages, which in turn are responsible for VCAM-1 upregulation by stromal/endothelial cells. VCAM-1/CD49d interactions result in an increased survival of CD49d-expressing CLL cells. Some of the molecules involved in the afore-mentioned network could be of interest as putative therapeutic targets (e.g. CD49d). Given these preliminary results, the following discussion will focus on the CD38 and CD49d surface distribution in CLL cells, and in particular on their association in the context of specific signaling areas of cell membranes (raft domains). Finally, the functional meaning beyond this supramolecular complex will be discussed introducing results of adhesion assays performed with CD49d engagement by VCAM-1 on CLL cells.